Effervescent composition, its production and use

Abstract

The present invention provides a water-soluble effervescent composition prepared by hot-melting (i) an active component and (ii) an acid and a carbonate for effervescing, both in powdery or granular state, with (iii) a water-soluble adjuvant whose melting point is not lower than 40 DEG C, for addition to drinking water.

What is claimed is: 
     
       1. A water-soluble effervescent composition comprising (i) a pyridone carboxylic acid synthetic antibacterial agent, (ii) an acid having an acid dissociation constant of 10 -5  or more and a carbonate for effervescing, both in a powdery or granular state, and (iii) a water-soluble adjuvant whose melting point is not lower than 40° C., which forms a discontinuous binder phase, wherein the amount of said adjuvant is from about 5 to about 25% by weight based on the weight of said composition, provided that when said antibacterial agent is also an effervescing acid then said active component may be used as said acid for effervescing. 
     
     
       2. The composition as claimed in claim 1, in admixture with drinking water. 
     
     
       3. The composition as claimed in claim 1, 90% or more of which passes through a 16 mesh screen. 
     
     
       4. The composition as claimed in claim 1, in which the solubility of the antibacterial agent in water at room temperature is 0.001% or more at pH 2.0 to 12.0. 
     
     
       5. The composition as claimed in claim 1, wherein the synthetic antibacterial agent is selected from the group consisting of benofloxacin, nalidixic acid, enoxacin, ofloxacin, amifloxacin, flumequine, tosfloxacin, piromidic acid, pipemidic acid, miloxacin, oxolinic acid, cinoxacin, norfloxacin, ciprofloxacin, pefloxacin, lomefloxacin, enrofloxacin, danofloxacin, binfloxacin, difloxacin, sarafloxacin, ibafloxacin, and salts thereof. 
     
     
       6. The composition as claimed in claim 1, wherein the synthetic antibacterial agent is selected from the group consisting of benofloxacin, enoxacin, ofloxacin, norfloxacin and salts thereof. 
     
     
       7. The composition as claimed in claim 1, wherein the acid for effervescing is an acid which is solid at room temperature and shows pH 4.5 or lower when saturated into water at room temperature, or its acid alkali metal salt. 
     
     
       8. The composition as claimed in claim 1, wherein the acid for effervescing is selected from the group consisting of tartaric acid, citric acid, maleic acid, fumaric acid, malic acid, adipic acid, succinic acid and their alkali hydrogen acid salts. 
     
     
       9. The composition as claimed in claim 1, wherein the carbonate for effervescing is a carbonate or a hydrogencarbonate of lithium, sodium, potassium or ammonium. 
     
     
       10. The composition as claimed in claim 1, wherein the water-soluble adjuvant is selected from the group consisting of polyethylene glycol, polypropylene glycol, polyoxyethylene-polypropylene copolymer, polyethylene ester and polyethylene sorbitan ester. 
     
     
       11. The composition as claimed in claim 1, wherein the melting point of the water-soluble adjuvant is 40° to 90° C. 
     
     
       12. The composition as claimed in claim 1, wherein the water-soluble adjuvant is polyethylene glycol having a molecular weight of about 4,000 to 12,000. 
     
     
       13. The composition as claimed in claim 1, which comprises about 0.1 to 50% by weight of the antibacterial agent, about 10 to 70% by weight of the carbonate for effervescing, an effective amount of the acid for effervescing to make a solution of the composition with a pH of about 2.0 to 12.0 and about 5 to 25% by weight of the water-soluble adjuvant, based on the weight of the composition. 
     
     
       14. The composition as claimed in claim 1, which comprises about 1 to 25% by weight of the antibacterial agent, about 20 to 40% by weight of the carbonate for effervescing, an effective amount of the acid for effervescing to make a solution of the composition with a pH of about 2.0 to 12.0 and about 10 to 15% by weight of the water-soluble adjuvant, based on the weight of the composition. 
     
     
       15. The composition as claimed in claim 1, wherein the antibacterial agent is a finely powdered synthetic antibacterial agent at least 80% of which passes through a 100 mesh screen and whose solubility is 0.001% or more at pH 2.0 to 12.0, the acid for effervescing is an acid at least 90% of which passes through a 30 mesh screen and which has an acid dissociation constant of 10 -3  or more and 40% RH or more critical humidity at 30° C., the carbonate for effervescing is sodium carbonate at least 90% of which passes through a 30 mesh screen and the water-soluble adjuvant has a melting point of 50° to 70° C. 
     
     
       16. The composition as claimed in claim 1, wherein the antibacterial agent is selected from the group consisting of benofloxacin, enoxacin and ofloxacin, the carbonate for effervescing is sodium carbonate, the acid for effervescing is selected from the group consisting of tartaric acid, citric acid, maleic acid and their sodium and potassium salts, and the water-soluble adjuvant is polyethylene glycol having a molecular weight of about 4000 to 12,000. 
     
     
       17. The composition as claimed in claim 1, which comprises benofloxacin, whose particle size is 150 μm or lower, L-tartaric acid whose particle size is 500 μm or lower, sodium carbonate whose particle size is 500 μm or lower, and polyethylene glycol having a molecular weight of about 6000. 
     
     
       18. A method for preparing a water-soluble effervescent composition, which comprises stirring a mixture of (i) a pyridone carboxylic acid synthetic antibacterial agent,(ii) an acid having an acid dissociation of 10 -5  or more and a carbonate for effervescing, both in a powdery or granular state, and (iii) a water-soluble adjuvant whose melting point is not lower than the melting point of the adjuvant, wherein the amount of said adjuvant is from about 5 to about 25% by weight based on the weight of said composition, and cooling the mixture to room temperature. 
     
     
       19. The method as claimed in claim 18, wherein the antibacterial agent is benofloxacin, the acid for effervescing is L-tartaric acid, the carbonate for effervescing is sodium carbonate, and the water-soluble adjuvant is polyethylene glycol having a molecular weight of about 6000. 
     
     
       20. The composition as claimed in claim 1, wherein the amount of the adjuvant is from about 8 to about 20% by weight based on the weight of the composition. 
     
     
       21. The composition as claimed in claim 1, wherein the amount of the adjuvant is from about 10 to about 15% by weight based on the weight of the composition.